查看更多>>摘要：Background and Aims: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malig-nancy that causes a poor survival. We aimed to identify its prognostic factors and to develop a nomogram that will pre-dict survival of ICC patients among all stages. Methods: A total of 442 patients with pathology-proven ICC registered at the Fifth Medical Center of PLA General Hospital between July 2007 and December 2019 were enrolled. Subjects were followed for survival status until June 30, 2020. A prognos-tic model visualized as a nomogram was constructed in the training cohort using multivariate cox model, and was then validated in the validation cohort. Results: The median age was 55 years. With a median follow-up of 50.4 months, 337 patients died. The median survival was 11.6 months, with 1-, 3- and 5-year survival rates of 48.3％, 22.7％ and 16.2％, respectively. Factors associated with overall survival were multiple tumors, lymph node involvement, vascular invasion, distant metastasis, decreased albumin, elevated lactate dehydrogenase (LDH), decreased iron, elevated fi-brinogen, elevated CA125 and elevated CA19-9. A nomo-gram predicting survival of ICC patients at the time of di-agnosis achieved a Harrel's c-statistic of 0.758, significantly higher than the 0.582 of the TNM stage alone. Predicted median survivals of those within the low, mid and high-risk subgroups were 35.6, 12.1 and 6.2 months, respectively. Conclusions: A nomogram based on imaging data and se-rum biomarkers at diagnosis showed good ability to predict survival in patients with all stages of ICC. Further studies are needed to validate the prognostic capability of our new model.
查看更多>>摘要：Background and Aims: Gallbladder polyp (GBP) assess-ment aims to identify the early stages of gallbladder car-cinoma. Many studies have analyzed the risk factors for malignant GBPs. In this retrospective study, we aimed to establish a more accurate predictive model for potential ne-oplastic polyps in patients with GBPs. Methods: We devel-oped a nomogram-based model in a training cohort of 233 GBP patients. Clinical information, ultrasonographic find-ings, and blood test findings were analyzed. Mann-Whitney U test and multivariate logistic regression analyses were used to identify independent predictors and establish the nomogram model. An internal validation was conducted in 225 consecutive patients. Performance and clinical bene-fit of the model were evaluated using receiver operating characteristic curves and decision curve analysis (DCA), re-spectively. Results: Age, cholelithiasis, carcinoembryonic antigen, polyp size, and sessile shape were confirmed as independent predictors of GBP neoplastic potential in the training group. Compared with five other proposed predic-tion methods, the established nomogram model presented better discrimination of neoplastic GBPs in the training co-hort (area under the curve [AUC]: 0.846) and the validation cohort (AUC: 0.835). DCA demonstrated that the greatest clinical benefit was provided by the nomogram compared with the other five methods. Conclusions: Our developed preoperative nomogram model can successfully be used to evaluate the neoplastic potential of GBPs based on simple clinical variables that maybe useful for clinical decision-making.
查看更多>>摘要：Background and Aims: With high rates of recurrence post-treatment, hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide and the major cause of cancer death. To improve the overall sur-vival of HCC patients, identification of a reliable biomarker and precise early diagnosis of HCC remain major unsolved problems. Methods: We initially screened data from the Cancer Genome Atlas liver cancer cohort to identify po-tential prognosis-related genes. Then, a meta-analysis of five international HCC cohorts was implemented to validate such genes. Subsequently, artificial intelligence models (random forest and neural network) were trained to predict prognosis accurately, and a log-rank test was performed for validation. Finally, the correlation between the molecular hepatocellular carcinoma prognostic score (mHPS) and the stromal and immune scoring in HCC were explored. Re-sults: A comprehensive list of 65 prognosis-related genes was obtained, most of which have been not extensively studied thus far. A universal HCC mHPS system depending on the expression pattern of only 23 genes was established. The mHPS system had general applicability to HCC patients (log-rank p<0.05) in a platform-independent manner (RNA sequencing or microarray). The mHPS was also correlated with the stromal and immune scoring in HCC, reflecting the status of the tumor immune microenvironment. Con-clusions: Overall, the mHPS is an easy and cost-effective prognosis predicting system, which can disclose previously uncovered heterogeneity among patient subpopulations. The mHPS system can further stratify patients who are at the same clinical stage and should be valuable for precise treatment. Moreover, the prognosis-related genes recog-nized in this study have potential in targeted and immune therapy.
查看更多>>摘要：Background and Aims: Hepatocellular carcinoma (HCC) is listed as one of the most common causes of cancer-related death. Oncolytic therapy has become a promising treatment because of novel immunotherapies and gene editing tech-nology, but biosafety concerns remain the biggest limitation for clinical application. We studied the the antitumor activ-ity and biosafety of the wild-type Newcastle disease virus HK84 strain (NDV/HK84) and 10 other NDV strains. Meth-ods: Cell proliferation and apoptosis were determined by cell counting Kit-8 and fluorescein isothiocyanate Annexin V apoptosis assays. Colony formation, wound healing, and a xenograft mouse model were used to evaluate in vivo and in vitro oncolytic effectiveness. The safety of NDV/HK84 was tested in nude mice by an in vivo luciferase imaging system. The replication kinetics of NDV/HK84 in normal tis-sues and tumors were evaluated by infectious-dose assays in eggs. RNA sequencing analysis was performed to explore NDV/HK84 activity and was validated by quantitative real-time PCR. Results: The cell counting Kit-8 assays of vi-ability found that the oncolytic activity of the NDV strains differed with the multiplicity of infection (MOI). At an MOI of 20, the oncolytic activity of all NDV strains except the DK/JX/21358/08 strain was >80％. The oncolytic activities of the NDV/HK84 and DK/JX/8224/04 strains were >80％ at both MOI=20 and MOI=2. Only NDV/HK84 had >80％oncolytic activities at both MOI=20 and MOI=2. We chose NDV/HK84 as the candidate virus to test the oncolytic effect of NDV in HCC in the in vitro and in vivo experiments. NDV/HK84 killed human SK-HEP-1 HCC cells without affecting healthy cells. Conclusions: Intratumor infection with NDV/HK84 strains compared with vehicle controls or positive controls indicated that NDV/HK84 strain specifically inhib-ited HCC without affecting healthy mice. High-throughput RNA sequencing showed that the oncolytic activity of NDV/HK84 was dependent on the activation of type I interferon signaling.
Jing CaoCuicui XiaoChrist-Jonathan Tsia Hin FongJiao Gong...
297-307页
查看更多>>摘要：Background and Aims: Long non-coding RNA small nucle-olar RNA host genes (SNHGs) play a critical role in the occur-rence and development of tumors. In this study, we aimed to investigate the role of SNHG4 in hepatocellular carcinoma (HCC) and its underlining mechanism. Methods: Datasets were acquired from The Cancer Genome Atlas (TCGA) data-base. lncLocator 2.0 was used to identify the distribution of SNHG4 in HCC cells. Gene expression, Kaplan-Meier surviv-al, microRNA and transcription factor target analyses were performed with the University of Alabama Cancer (UALCAN) Database, Kaplan-Meier Plotter, LinkedOmics, WebGestalt and gene set enrichment analysis, respectively. Gene On-tology and pathway enrichment analyses and assessment of RNA binding proteins were performed by R software, circlncRNAnet and Encyclopedia of RNA Interactomes (EN-CORI). In addition, CirclncRNAnet and ENCORI were used to find the correlation between SNHG4 and important proteins, while the prognostic value was assessed with the Human Protein Atlas database and Kaplan-Meier Plotter. Results:Expression of SNHG4 in HCC is higher in HCC tissue than in normal healthy liver tissues and is mainly distributed in the nucleus. SNHG4 positively correlated with poor prognosis (p<0.01 for overall survival and recurrence-free survival). Functional enrichment analysis revealed SNHG4 involve-ment with regulation of ribosomal RNA synthesis and the RNA processing and surveillance pathway. SNHG4 is closely associated with miR-154 and miR-206, transcription factor target E2F family and the signaling pathway for MAPK/ERK and mTOR. U2 auxiliary factor 2 (U2AF2) showed strong correlation with SNHG4, while low-expression of U2AF2 showed good prognosis. Conclusions: Based on our find-ings, we infer SNHG4 may play a role in the formation of HCC via regulation of tumor-related pathways.
查看更多>>摘要：Background and Aims: Numerous studies have explored the important role of N6-methyladenosine (m6A) in cancer. Nonetheless, the interaction between m6A and long noncod-ing RNAs (lncRNAs) is poorly investigated. Herein, we system-atically analyzed the role and prognostic value of m6A-related lncRNAs in hepatocellular carcinoma (HCC). Methods: The m6A-related lncRNAs were identified based on the correlation coefficients with m6A-related genes in HCC from The Cancer Genome Atlas. Subsequently, a novel risk score model was determined using the least absolute shrinkage and selection operator Cox regression analyses. Univariate and multivari-ate Cox analyses were used to identify independent prog-nostic factors for overall survival (OS) of HCC; thereafter, a prognostic nomogram was constructed. Results: A total of 259 lncRNAs showed significant correlations with m6A in HCC, while 29 lncRNAs had prognostic significance. Further, six critical m6A-related lncRNAs (NRAV, SNHG3, KDM4A-AS1, AC074117.1, AC025176.1, and AL031985.3) were screened out to construct a novel risk score model which classified HCC patients into high- and low-risk groups. Survival analy-ses revealed that patients in the high-risk group exhibited worse OS, both in the training and validation groups. The risk score was also identified as an independent prognostic factor of OS, and a nomogram was established and verified with superior prediction capacity. Besides, the risk score signifi-cantly correlated with the expression of immune checkpoint genes and immune subtypes. Conclusions: These findings indicated the significant role of m6A-related lncRNAs in HCC and the potential application of the novel risk score model for prognostic prediction.
查看更多>>摘要：Defects in mitochondria are responsible for various ge-netic and acquired diseases. Mitochondrial transplantation, a method that involves introduction of healthy donor mi-tochondria into cells with dysfunctional mitochondria, could offer a novel approach to treat such diseases. Some studies have demonstrated the therapeutic benefit of mitochondrial transplantation and targeted delivery in vivo and in vitro within hepatocytes and the liver. This review discusses the issues regarding isolation and delivery of mitochondria to hepatocytes and the liver, and examines the existing litera-ture in order to elucidate the utility and practicality of mito-chondrial transplantation in the treatment of liver disease. Studies reviewed demonstrate that mitochondrial uptake could specifically target hepatocytes, address the challenge of non-specific localization of donor mitochondria, and pro-vide evidence of changes in liver function following injection of mitochondria into mouse and rat disease models. While potential benefits and advantages of mitochondrial trans-plantation are evident, more research is needed to deter-mine the practicality of mitochondrial transplantation for the treatment of genetic and acquired liver diseases.
查看更多>>摘要：Nonalcoholic fatty liver disease (NAFLD) is a multisystemic clinical condition that presents with a wide spectrum of ex-trahepatic manifestations, such as obesity, type 2 diabe-tes mellitus, metabolic syndrome, cardiovascular diseases, chronic kidney disease, extrahepatic malignancies, cogni-tive disorders, and polycystic ovarian syndrome. Among NAFLD patients, the most common mortality etiology is cardiovascular disorders, followed by extrahepatic malig-nancies, diabetes mellitus, and liver-related complications. Furthermore, the severity of extrahepatic diseases is par-allel to the severity of NAFLD. In clinical practice, aware-ness of the associations of concomitant diseases is of major importance for initiating prompt and timely screening and multidisciplinary management of the disease spectrum. In 2020, a consensus from 22 countries redefined the disease as metabolic (dysfunction)-associated fatty liver disease (MAFLD), which resulted in the redefinition of the corre-sponding population. Although the patients diagnosed with MAFLD and NAFLD mostly overlap, the MAFLD and NAFLD populations are not identical. In this review, we compared the associations of key extrahepatic diseases between NAFLD and MAFLD.
查看更多>>摘要：Non-alcoholic fatty liver disease (NAFLD) is closely related to insulin resistance, type 2 diabetes mellitus, and obesity. It is nowadays considered a multisystem disease with a strong as-sociation with cardiovascular disease and arterial hyperten-sion, which interfere with changes in the coagulation system. Coagulation disorders are common in patients with hepatic impairment and are dependent on the degree of liver dam-age. Patients with NAFLD may have preserved overall he-mostatic profile, but many studies suggest a trend toward a procoagulant state. Hypercoagulable state in NAFLD patients may even induce progression of hepatic injury. Endothelial dysfunction is present in the systemic and portal vein circu-lation in NAFLD patients, and platelets are being recognized as modulators of liver diseases through various mechanisms. Through a literature review, we discuss possible disorders in the coagulation cascade and fibrinolysis, endothelial dys-function, and platelet abnormalities in patients with NAFLD. Considering the processes and mechanisms involved in the hemostatic abnormalities associated with NAFLD, directly related to liver disease or indirectly related through inflam-matory processes and metabolic disorders, several potential therapeutic targets have been identified and reviewed here. Citation of this article: Ogresta D, Mrzljak A, Cigrovski Berkovic M, Bilic-Curcic I, Stojsavljevic-Shapeski S, Virovic-Jukic L. Coagulation and Endothelial Dysfunction Associated with NAFLD: Current Status and Therapeutic Implications.
查看更多>>摘要：The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide, reflecting the current epidemics of obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. NAFLD is characterized by the accu-mulation of fat in the liver, and is known to be a cause of cir-rhosis. Although many pathways have been proposed, the cause of NAFLD-linked fibrosis progression is still unclear, which posed challenges for the development of new thera-pies to prevent NASH-related cirrhosis and hepatocellular carcinoma. Cirrhosis is associated with activation of hepatic stellate cells (HSC) and accumulation of excess extracellular matrix proteins, and inhibiting the activation of HSCs would be expected to slow the progression of NAFLD-cirrhosis. Multiple molecular signals and pathways such as oxidative stress and glutaminolysis have been reported to promote HSC activation. Both mechanisms are plausible antifibrotic targets in NASH, as the activation of HSCs the proliferation of myofibroblasts depend on those processes. This review summarizes the role of the glutaminolysis-ammonia-urea cycle axis in the context of NAFLD progression, and shows how the axis could be a novel therapeutic target.
NETL
NSTL
万方数据
维普